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Purpose: The administration frequency of intravitreal anti‐vascular endothelial growth factor (anti‐VEGF) in neovascular age‐related macular degeneration (AMD) have been widely discussed. The primary objective of the study was to explore the association between anatomical outcomes and changes in functional outcome. Methods: This was a retrospective cohort study of patients with newly diagnosed neovascular AMD with a minimum of 12 months of follow‐up. Only one eye per patient was included. Patients were treated according to the observe‐and‐plan or the pro‐re‐nata regimen. All patients were regularly examined from the time of diagnosis up to 24 months. The effect of intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelium detachment (PED) at any time point on visual acuity (VA) was tested, as well as the long‐term effect and the risk of losing VA. Further, the variability of central retinal thickness (CRT) was calculated for each eyes' individual measures during the observation period, excluding the monthly loading phase. The prognostic effect of each factor on VA was estimated by regression analysis. The primary outcome measure was VA, which was correlated with the presence or absence of fluid, seen as IRF, SRF or PED. Results: A total of 504 treatment naïve eyes from 504 patients was included. The presence of IRF was associated with lower VA at all visits (p < 0.001). However, the presence of SRF or PED was not significantly associated with worse VA at any time point during the observation period. Patients in the upper quartile of CRT variance had a greater loss in VA after 12 and 24 months (p < 0.001). Conclusions: In this retrospective cohort study, the presence of intraretinal fluid was associated with poorer visual outcome in neovascular AMD patients treated with anti‐VEGF, but the presence of subretinal fluid and PEDs was not. This suggests that IRF is worse than subretinal fluid and PEDs for AMD outcomes and therefore requires the most intensive treatment. Further, we found that patients with the highest CRT variability during the study period had poorer visual outcomes after 12 and 24 months, indicating that stringent control of retinal fluid volume fluctuations is important to prevent visual acuity decline over time. [ABSTRACT FROM AUTHOR]

Purpose: Chemokines are a group of cytokines that guide immune cell migration. We studied plasma levels of inflammatory chemokines in patients with polypoidal choroidal vasculopathy (PCV) and compared with healthy age‐matched control individuals. Methods: This was a clinic‐based prospective case–control study of participants (n = 60) with either PCV (n = 26) or age‐matched healthy controls (n = 34). We sampled fresh venous blood and isolated plasma for analysis. We used U‐PLEX Human Assays to quantify concentrations of the inflammatory chemokines MCP‐1/CCL2, RANTES/CCL5, eotaxin/CCL11, IP‐10/CXCL10 and fractalkine/CX3CL1. Results: Plasma levels of fractalkine was significantly higher in patients with PCV when compared to healthy controls (mean ± SD: 7291 ± 2461 pg/ml versus 5879 ± 2001 pg/ml; p = 0.021). Plasma levels of MCP‐1 (p = 0.846), RANTES (p = 0.288), eotaxin (p = 0.496) and IP‐10 (p = 0.352) did not differ significantly between the groups. To evaluate possible biomarker quality of fractalkine, we used a ROC analysis and found a positive but weak discriminatory ability (AUC = 0.68). Conclusion: Patients with PCV have a higher plasma level of fractalkine. Although the differences do not possess strong biomarker qualities, they inform on disease processes of a poorly understood disease and suggest that the fractalkine‐CX3CR1 axis may be involved. As this study did not investigate local chemokine concentrations, we are unable to confirm or disprove any local chorioretinal interaction, and our findings should be interpreted with such caution. [ABSTRACT FROM AUTHOR]

Age‐related macular degeneration (AMD) is the most common cause of visual impairment in the developed world. A number of patients experience complex lifelike visual experiences—Charles Bonnet syndrome (CBS). In this systematic review, our aim was to provide an overview of the CBS literature in relation to AMD, to determine the prevalence of CBS in patients with AMD and to provide an overview of associated demographical and clinical aspects. We searched the literature databases PubMed/MEDLINE, EMBASE, Web of Science, the Cochrane Central, and PsycINFO on 22 March 2019 for studies evaluating the prevalence of CBS in patients with AMD. Two independent authors extracted the data and evaluated risk of bias. Studies were reviewed qualitatively in the text and quantitatively in a meta‐analysis including subgroup analyses for differences between demographic and clinical factors. We identified 18 studies with data on >4303 patients with AMD. We found an overall prevalence of CBS of 15.8% (95% confidence interval: 11.0%–21.2%). When looking at consecutively recruited patients with neovascular AMD from the clinic, prevalence of CBS was 7.2% (95% confidence interval: 4.3%–10.6%). Among visitors to visual rehabilitation centres, prevalence of CBS was 31.6% (95% confidence interval: 21.7%–42.3%). Taken together, we find that CBS is rather common in patients with AMD. [ABSTRACT FROM AUTHOR]

Purpose: Tissue inhibitor of metalloproteinase (TIMP) is known to play a role in age‐related macular degeneration (AMD). We wished to investigate alterations in different late stages of AMD: neovascular AMD and geographic atrophy (GA). Methods: This was a prospective case–control study. A total of 125 participants were included consecutively during a period of 18 months. We included 46 patients with neovascular AMD, 46 patients with GA without any sign of choroidal neovascularization in either eye, and 33 healthy aged controls. Patients with immune‐affecting disorders were not included. Commercial immunoassay kits were used to quantify levels of TIMP‐1, TIMP‐3, MMP‐2 and MMP‐9 in blood plasma. Results: We found that patients with neovascular AMD had lower plasma concentration of TIMP‐3 (p = 0.028) than healthy controls. Patients with GA had higher plasma levels of TIMP‐1 (p < 0.001) and MMP‐9 (p = 0.022) compared to healthy controls. Also, we found that TIMP‐1 levels in patients with GA increased with age (Spearman's rho = 0.04, p = 0.006). Conclusion: Matrix metalloproteinases (MMPs) and TIMPs, which are known to be involved in age‐related changes in Bruch's membrane, are significantly altered systemically, suggesting the presence of an imbalance in the homeostasis of the extracellular matrix. These imbalances may explain differences in the clinical manifestation of late AMD. [ABSTRACT FROM AUTHOR]

Purpose: Ageing is the strongest predictor of neovascular age‐related macular degeneration (AMD), where neuroinflammation is known to play a major role. Less is known about polypoidal choroidal vasculopathy (PCV), which is an important differential diagnosis to neovascular AMD. Here, we report plasma markers of inflammation with age (inflammaging) in patients with PCV, patients with neovascular AMD and a healthy age‐matched control group. Methods: We isolated plasma from fresh venous blood obtained from participants (n = 90) with either PCV, neovascular AMD, or healthy maculae. Interleukin(IL)‐1β, IL‐6, IL‐8, IL‐10 and tumour necrosis factor receptor 2 (TNF‐R2) were measured using U‐PLEX Human Assays. Routine plasma C‐reactive protein (CRP) was measured using Dimension Vista 1500. Results: Patients with PCV had plasma levels of IL‐1β, IL‐6, IL‐8, IL‐10 and TNF‐R2 similar to that in healthy controls. Patients with neovascular AMD had significantly higher plasma IL‐1β, IL‐6 and IL‐10 than healthy controls, whereas no significant differences were observed for plasma IL‐8 and TNF‐R2. Differences between plasma IL‐1β, IL‐6 and IL‐10 possessed a positive but weak ability in discriminating neovascular AMD from PCV. Both patients with PCV and patients with neovascular AMD had significantly higher levels of routine plasma CRP. Conclusion: Patients with PCV differ from patients with neovascular AMD in terms of plasma inflammaging profile. Apart from increased CRP, no signs of inflammaging were observed in patients with PCV. In patients with neovascular AMD, we find a specific angiogenesis‐twisted inflammaging profile. [ABSTRACT FROM AUTHOR]

Importance Geographic atrophy (GA) is a progressing atrophy of the neuroretina with no treatment option. Background: Age‐related malfunction of retinal microglia amplifies response towards age‐related tissue stress in age‐related macular degeneration. Here, we investigated monocyte CD200 expression – the circulating middleman negotiating retinal microglial activity – in a poorly understood subtype of age‐related macular degeneration. Design Prospective case–control study. Participants: Forty‐six patients with GA and 26 healthy controls were included. Methods: All participants were subjected to a structured interview and detailed retinal examination. Controls were recruited from patient's spouses accompanying them in the clinic to match the groups best possibly. Participants had no history of immune disorders or cancer, and did not receive any immune‐modulating medication. Patients did not have any history or sign of choroidal neovascularization in either eye. Fresh drawn blood was stained with monoclonal antibodies and prepared for flow cytometry to evaluate CD200 expression in monocytes and their functional subsets. Main Outcome Measures: The percentage of CD200+ monocytes in patients and controls. Results: We found that monocytes were more CD200 positive in patients with GA compared to healthy age‐matched controls. Then, we explored the potential relationship between CD200 expression and important fundus autofluorescence patterns that predict disease progression. Patients with a high risk of progression (patients with high degree of hyperautofluorescence) had distinctly increased CD200 expression compared to other patients with GA. Conclusions and Relevance: Our data reveals that abnormal monocytic CD200 expression is present in GA, and in particular among those identified as fast progressors. [ABSTRACT FROM AUTHOR]

Abstract: Background: We investigated the expression of chemokine receptors CCR2 (C‐C chemokine receptor) 2 and CX3CR1 (C‐X3‐C receptor 1) on circulating monocyte subsets in patients with neovascular age‐related macular degeneration (AMD) and patients with polypoidal choroidal vasculopathy (PCV). Methods: We recruited patients with neovascular AMD, patients with PCV and age‐matched healthy controls for this prospective case–control study. All participants underwent comprehensive clinical examination and imaging. Freshly sampled venous blood was prepared for flow cytometry, where we determined the proportion of CCR2+‐ and CX3CR1+‐positive cells in monocyte subsets identified using monocyte identification and subgrouping surface markers CD14, CD16 and HLA‐DR. Results: Patients with neovascular AMD had significantly increased proportion of CCR2+ and CX3CR1+ non‐classical monocytes. PCV type 1 was associated with significantly increased CCR2+ and CX3CR1+ in all monocyte subsets when compared to PCV type 2. Conclusions: Neovascular AMD is associated with increased expression of angiogenesis‐associated chemokine receptors in the pro‐inflammatory non‐classical monocytes. PCV differs from neovascular AMD immunologically and show immunological heterogeneity across angiographic subtypes. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a prevalent disease with progressive loss of neuroretina. Age-related macular degeneration (AMD) holds similarities with other complex neurodegenerative diseases, such as Alzheimer's, strongly illustrated by (1) involvement of progressive dysregulation and deterioration of multiple signalling pathways, (2) temporal accumulation of proinflammatory lesions, (3) insidious inflammatory neurodegeneration leading to neural cell atrophy and death and to progressive loss of function. We hypothesized that an immunological neurodegenerative drive could be present in late AMD and that this neurodegenerative drive would be reflected in NfL levels since this test is sensitive to even low levels of neurodegeneration. [Extracted from the article]

Purpose: Interleukin-8 (IL-8) is a potent pro-angiogenic and pro-inflammatory chemokine, suggested to hold a role in neovascular age-related macular degeneration (nAMD). Our aim is to study the association of the single-nucleotide polymorphism -251 A/T (rs4073) in the IL-8 promoter region with the treatment response to intravitreal anti-vascular endothelial growth factor (VEGF) injections in nAMD., Patients and Methods: This is a prospective study of treatment-naïve patients with nAMD. Treatment response after a loading dose of three intravitreal anti-VEGF injections was defined as functional response based on change in visual acuity, and morphological response based on change in central retinal thickness (CRT) and intraretinal fluid on optical coherence tomography. Morphological response was categorized in good, partial, and poor responders. Blood DNA was analyzed for -251 A/T genotype., Results: The IL-8 promoter polymorphism -251 A/T was not significantly associated to functional treatment response ( P =0.09). No significant association was found between genotype and morphological treatment response ( P =0.799). Older age was significantly associated to good morphological responders compared to partial and poor responders ( P =0.014)., Conclusion: The IL-8 polymorphism -251 A/T is not associated to morphological nor functional treatment response to intravitreal anti-VEGF injections in patients with nAMD., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Thomsen et al.)

Background: We investigated the expression of chemokine receptors CCR2 (C-C chemokine receptor) 2 and CX3CR1 (C-X3-C receptor 1) on circulating monocyte subsets in patients with neovascular age-related macular degeneration (AMD) and patients with polypoidal choroidal vasculopathy (PCV)., Methods: We recruited patients with neovascular AMD, patients with PCV and age-matched healthy controls for this prospective case-control study. All participants underwent comprehensive clinical examination and imaging. Freshly sampled venous blood was prepared for flow cytometry, where we determined the proportion of CCR2 + - and CX3CR1 + -positive cells in monocyte subsets identified using monocyte identification and subgrouping surface markers CD14, CD16 and HLA-DR., Results: Patients with neovascular AMD had significantly increased proportion of CCR2 + and CX3CR1 + non-classical monocytes. PCV type 1 was associated with significantly increased CCR2 + and CX3CR1 + in all monocyte subsets when compared to PCV type 2., Conclusions: Neovascular AMD is associated with increased expression of angiogenesis-associated chemokine receptors in the pro-inflammatory non-classical monocytes. PCV differs from neovascular AMD immunologically and show immunological heterogeneity across angiographic subtypes., (© 2018 Royal Australian and New Zealand College of Ophthalmologists.)